The major aim of this proposal is to define the axonal projections and interactions of rostral and caudal ventrolateral medullary (VLM) neurons specifically involved in the tonic and reflex control of sympathetic nerve discharge (SND) and blood pressure. Considerable interest has recently focused on the role of the VLM in the control of blood pressure and in the genesis of some forms of hypertension. Neurons in the rostral and caudal VLM appear to provide excitatory and inhibitory influences, respectively, on the activity of the sympathetic innervation to the heart and vasculature. Computer-aided analyses (spike-triggered averaging and post-R wave analysis) are used to identify VLM neurons with spontaneous activity correlated to SND in the Dial-urethane anesthetized cat. A ventricular pacing test is used to separate such neurons into two groups: neurons in an efferent sympathetic network (sympathetic neurons) and inteneurons in the afferent limb of the baroreceptor reflex arc. The responses to activation of the baroreceptor and chemoreceptor reflexes are used to determine the function (excitation or inhibition) of VLM neurons in efferent sympathetic pathways. Microstimulation of autonomic nuclei in the spinal cord and various brain regions (e.g., nucleus parabrachialis and locus coeruleus in the pons and paraventricular nucleus in the hypothalamus) are used to define the axonal projection sites of VLM neurons that control background activity in sympathetic nerves and thus resting blood pressure. Microstimulation is also used to determine brain regions that provide excitatory and inhibitory inputs to these neurons. Crosscorrelation analysis is used to characterize the interactions among rostral and caudal VLM neurons that control SND. Pharmacological studies are planned to assess whether epinephrine- and norepinephrine-containing neurons in the rostral an caudal VLM are involved in the tonic and reflex control of SND. For this purpose the responses to electrical stimulation and electrolytic lesions of the rostral or caudal BLM will be compared in control cats and in cats treated with drugs that block the synthesis of epinephrine or norepinephrine. The responses of VLM sympathetic neurons to iontophoresis of these catecholamines and adrenergic blocking agents will also be studied.